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IFI16 encodes a nucleic acid-sensor which detects latent EBV and triggers inflammasome activation. We analysed IFI16 variants in two multiple sclerosis (MS) case-control cohorts from Italy and Spain; results were combined with a previous study. A risk variant for celiac disease/rheumatoid arthritis, a polymorphic exon 7 duplication, and a copy number variant (CNV) in the 5' region were genotyped. No significant association was detected, although heterogeneity was noted for the 5' CNV in the Italian plus GeneMSA cohorts and the Spanish sample. Thus, IFI16 variants do not contribute to MS susceptibility, although some heterogeneity may exist for the 5' CNV., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Specific polymorphisms within the vascular endothelial growth factor (VEGF) gene promoter region are of particular interest: VEGF variability has been associated with increased risk of developing a wide variety of disorders from diabetes to neurodegenerative diseases, suggesting functions not confined to its originally described vascular effects. A hypothetical loss of the VEGF-mediated neuroprotective effect has been proposed as a cause of neurodegenerative disorders. An impaired regulation of VEGF expression has been also reported in Alzheimer's disease (AD) pathogenesis. Recently, VEGF gene promoter polymorphisms have been associated with an increased risk for AD in the Italian population. Conversely, two subsequent studies failed to find a positive association between VEGF variability and greater risk for AD. To better clarify this issue, a meta-analysis of all published association studies has been performed. Overall, polymorphic variants within VEGF gene promoter confer greater risk for AD at least in the Italian population; the meta-analysis provides evidence of a role of the functional variant C(-2578)A in the pathogenesis of the disease, although the pooled odds ratio obtained represents a modest effect. These findings provide new evidence for an additional candidate genetic risk factor for AD that can be tested in further studies.